The purpose of these studies is to investigate the ability of cannabinoids to be neuroprotective during an ischemic event. Recent studies conducted in this area have generally focused on a single neuron type and have been inconclusive. However, data exists suggesting that the cannabinoid CB1 receptor is differentially expressed in distinct brain regions. Furthermore, coupling of CB1 receptors to G-proteins may also differ in different brain regions, and the signal transduced varies depending on the agonist. Therefore the questions addressed in this proposal are: 1. Does CB1 receptor expression differ in hippocampal, cerebellar granule neuron and cerebrocortical neuron cultures? Moreover, what are the binding affinities and efficacies of a variety of cannabinoid agonists in these cultures? 2. Will different cannabinoid agonists exert a neuroprotective action from hypoxiainduced excitotoxicity in these cultures? 3. Does reduced hypoxia-induced glutamate release correlate with a neuroprotective action in cannabinoid treated cultures? 4. Do cannabinoids influence excitotoxicity-induced calcium influx in each of these neuron types? Answering these questions will broaden our understanding of how cannabinoids may be used for the treatment of ischemic events or other neurodegenerative diseases attributed to excitotoxicity.